The long range objective of this project is to carefully re-examine the nature of binding specificity at antibody combining regions and other types of receptor sites. The effects of polyvalent binding on binding energy and specificity will be considered, and together these properties will be related to the behavior of immune systems. In particular, multispecific binding of disparate structures by individual antibody species is being studied through screening of specifically purified, radiolabeled antibodies with affinity chromatography columns. The ligands are bound to these columns using large haptenic reagents synthesized especially for this purpose using methods of peptide synthesis. Multispecific binding will be used for producing and isolating homogeneous antibody by cross-stimulation and immunoadsorption. The resulting preparations will be studied by amino acid sequencing in order to gain more insight into the nature of antibody diversity. Methods for improving sequence analysis are actively being pursued. A number of chemical techniques and products that have been developed from the above work are being used in collaborative studies on molecular interpretations of cellular mechanisms in immune responses. Materials employed include synthetic thymus-independent antigens.